Kidney transplantation is the treatment of choice for most causes of end stage renal disease. However, current methods for transplantation rely upon the chronic use of immunosuppressive drugs to prevent immune rejection of the transplanted organ. These drugs are not completely effective such that many recipients eventually lose allograft function due to either acute or chronic rejection. They also are associated with metabolic, infectious and neoplastic side effects. Importantly, standard immunosuppressive approaches also are thought to inhibit adaptive immune processes promoting organ acceptance. This later effect makes transplant recipients dependent on immunosuppression for life. Recent clinical trials have shown that a patients'dependence on chronic immunosuppression can be reduced by peritransplant treatment with alemtuzumab, a monoclonal antibody that transiently depletes T-cells. Preclinical data also have indicated that, unlike conventional immunosuppressive therapy, drugs that inhibit T-cell costimulation, for example, by interfering with the molecules CD80 and CD86, promote adaptation of the immune system such that immunosuppressive requirements diminish with time. In some animal models, this has led to allograft tolerance, a condition in which a transplanted organ is accepted without the need for chronic immunosuppression and without recipient immunoincompetence. This process has been shown in animal models to be facilitated by the mTOR inhibitor sirolimus, and to be aided by the infusion of donor blood or bone marrow. This study will combine lymphocyte depletion, mTOR inhibition, and costimulation blockade, in 20 renal allograft recipients, to determine whether together these therapies will promote allograft acceptance. Peritransplant T-cell depletion induced by alemtuzumab will be used in combination with chronic therapy with the mTOR inhibitor sirolimus in combination with belatacept, a novel fusion protein specific for the costimulation molecules CD80 and CD86. Ten patients in this trial also will receive an infusion of donor bone marrow to determine if this additional therapy will further facilitate tolerance. All patients will be given a single dose of alemtuzumab on the day of transplantation. All patients then will be treated with belatacept and sirolimus for 1 year. Ten patients will be randomized to receive a single dose of donor bone marrow 7 days after transplantation. Patients who remain rejection free for 1 year will be gradually withdrawn from sirolimus then, based on specific biopsy criteria, be discontinued from belatacept to determine if they are tolerant to their grafts. In addition to clinical outcome, immune reconstitution following T-ceIl depletion and the development of donor-specific immune unresponsiveness will be evaluated. If successful, the trial will present an applicable method for transplantation without dependence on chronic immunosuppressive drugs.